MATERIALS & METHODS (continued) ADA EXPOSURE • “Overall exposure to ADA” (outside of and within the registry) was calculated as time from the initial (first ever) ADA dose to 14 days after the last ADA dose in the registry, excluding the total number of days of treatment interruption in the registry. • “Registry exposure to ADA” (within the registry) was calculated as time from first ADA dose in the registry to 14 days after the last ADA dose in registry, excluding the total number of days of treatment interruption in the registry. • A treatment interruption (TI) is defined as >70 days without any ADA dose; TI starts at day 71 after ADA was stopped. SAFETY • All treatment-emergent AEs (All-TEAEs) were events occurring from the date of initial (first ever) ADA dose through 70 days after the date of the last ADA dose in the registry, excluding AEs occurring during TIs. This included AEs collected in the registry, collected retroactively before registry entry, and from feeder studies for patients rolling over from preregistry feeder clinical trials. • Incidence rates for All-TEAEs are reported as events per 100 patient-years (E/100PY) of overall exposure to ADA. • Standardized mortality ratio (SMR): – SMR was calculated as the ratio of observed to expected treatment- emergent deaths using the 2006 country-specific World Health Organization mortality rates. – An SMR <1.0 indicates that the observed number of deaths is lower than the expected rate in an age-, sex-, and country-matched general population. EFFECTIVENESS • The proportion of patients achieving Physician Global Assessment (PGA) score of “clear” or “minimal” were analyzed as observed during registry participation (patients were not necessarily receiving ADA at the time of assessment). RESULTS • This 8-year interim analysis used data collected from 6045 patients (2554 New-Rx patients, 42.2%) who were enrolled and dosed between 26 September 2008 and 30 November 2016 (Table 1). • The majority of patients in ESPRIT were from sites in the United States (69.5%) and Canada (13.9%). Table 1. Patient Demographics and Disease Characteristics at Registry Entry (All-Rx and New-Rx Patient Populations) Demographic or Characteristic All-Rx N=6045 New-Rx N=2554 Sex Male, n (%) 3485 (57.7) 1376 (53.9) Female, n (%) 2560 (42.3) 1178 (46.1) Racea, n (%)* White 5268 (87.3) 2221 (87.0) Black 178 (2.9) 65 (2.5) Asian 259 (4.3) 106 (4.2) American Indian/Alaska native 16 (0.3) 7 (0.3) Native Hawaiian or other Pacific Islander 40 (0.7) 25 (1.0) Other 251 (4.2) 116 (4.5) Multi-race 22 (0.4) 12 (0.5) Age, y, median (range) 47 (18–94) 46 (18–91) Weight, kg, median (range)* 87.0 (41.0–252.0)b 86.0 (41.0–218.0)c BMI, kg/m2, median (range) 29.4 (16.0–76.8)d 29.4 (16.0–69.9)e Psoriatic arthritis, n (%)* Not analyzedf 868 (34.1)g Family history of psoriasis, n (%)* Not analyzedf 1067 (41.9)h Duration of psoriasisi, y, median (range) Not analyzedf 13.4 (0–68.0)h PGAj, n (%)* Clear 733 (12.2) 53 (2.1) Minimal 1176 (19.5) 140 (5.5) Mild 1150 (19.2) 312 (12.3) Moderate 1778 (29.5) 1117 (43.9) Severe 973 (16.1) 748 (29.4) Very severe 213 (3.5) 172 (6.8) *Percentages calculated on non-missing values. aMissing data: All-Rx, n=11; New-Rx, n=2. bn=5931; cn=2497; dn=5912; en=2492. fNot analyzed because not all data were captured in the registry database. gn=2549; hn=2547. iCalculated at registry entry. jMany patients had received ADA before entering the registry, demonstrated by the number of patients entering the registry with a PGA score of “clear” or “minimal.” Missing data: All-Rx, n=22; New-Rx, n=12. ADA=adalimumab; All-Rx=all-treated patient population; BMI=body mass index; New-Rx=new prescription patient population; PGA=Physician Global Assessment. • 3662 (60.6%) All-Rx and 1372 (53.7%) New-Rx patients are continuing in the registry as of 30 November 2016. – Of those, 2494 (41.3%) All-Rx and 791 (31.0%) New-Rx patients have not permanently discontinued ADA. – Of those, 1688 (27.9%) All-Rx and 497 (19.5%) New-Rx patients have never interrupted ADA treatment for >70 days or permanently discontinued ADA. • 2383 (39.4%) All-Rx and 1182 (46.3%) New-Rx patients discontinued from the registry; the most frequent reason for discontinuation was being lost to follow-up (18.2%, All-Rx and 23.9%, New-Rx; Table 2). Table 2. Reasons for Discontinuation from Registry and Registry Drug (All-Rx and New-Rx Patient Populations) Reason for Discontinuation (in >1% Patients) All-Rx N=6045 n (%) New-Rx N=2554 n (%) From registrya, any reason 2383 (39.4) 1182 (46.3) Lost to follow-up 1100 (18.2) 611 (23.9) Withdrew consent 521 (8.6) 219 (8.6) Lack of efficacy 98 (1.6) 63 (2.5) Death 95 (1.6) 36 (1.4) Patient moved 98 (1.6) 39 (1.5) Noncompliant 98 (1.6) 64 (2.5) Other 472 (7.8) 189 (7.4) From registry drugb, any reason 3551 (58.7) 1763 (69.0) Lack of efficacy 1286 (21.3) 692 (27.1) Lost to follow-up 757 (12.5) 407 (15.9) Withdrew consent 376 (6.2) 152 (6.0) AE 188 (3.1) 95 (3.7) SAE or SAE of interest 114 (1.9) 47 (1.8) Other 778 (12.9) 333 (13.0) aReasons for registry discontinuations in ≤1% of patients were AE, intolerance, SAE or SAE of interest, satisfactory improvement, pregnancy, or unknown. bReasons for registry drug discontinuations in ≤1% of patients were intolerance, patient moved, satisfactory improvement, patient death, noncompliance, pregnancy, required additional therapy, or unknown. AE=adverse event; All-Rx=all-treated patient population; New-Rx=new prescription patient population; SAE=serious AE. • Median (range) duration of overall exposure to ADA was 1430 (14–5161) and 657.5 (14–2947) days for All-Rx and New-Rx patient populations, respectively. • Median (range) duration of registry exposure to ADA was 1077 (14–2947) and 656 (14–2947) days for All-Rx and New-Rx patient populations, respectively. • The number of patients according to duration of overall exposure to ADA and registry exposure to ADA are shown in Figure 2. Figure 2. Number of Patients Based on Duration of ADA Exposure (All-Rx and New-Rx Patient Populations) 0188413396621936New-Rx, N=2554 0191412396626New-Rx, N=2554 929 1274 1304 1013 1115All-Rx, N=6045 All-Rx, N=6045 1740 1316 1187 1372 ≤1 y >1 to 3 y >3 to 5 y >5 to 7 y 1015 430 >7 to 9 y 324 >9 y ≤1 y >1 to 3 y >3 to 5 y >5 to 7 y >7 to 9 y >9 y 0 Number of patients based on their overall exposure to ADA (outside of and within the registry) Number of patients based on their registry exposure to ADA (within the registry) ADA=adalimumab; All-Rx=all-treated patient population; New-Rx=new prescription patient population. • Time to discontinuation from the registry and from registry drug in All-Rx and New-Rx patients is shown in Figure 3. Figure 3. Time to Discontinuation From the Registry and From Registry Drug (ADA, All-Rx, and New-Rx Patient Populations) 0 0.0 0.1 0.2 0.4 0.6 0.8 1.0 Monthsa P ro b a b ili ty o f R e m a in in g in t h e R e g is tr y o r o n R e g is tr y D ru g Continuations Patients Total, N Failed, n Censored, n (%) Registry 6045 2383 3662 (60.6) Registry Drug 6045 3551 2494 (41.3) 12 24 36 48 60 72 84 96 All-Rx New-Rx All-Rx New-Rx Registry 2554 1182 1372 (53.7) Registry Drug 2554 1763 791 (31.0) aTime of observation (first day to last day of registry participation) was used for time to registry discontinuation; registry exposure to adalimumab was used for time to registry drug discontinuation. All-Rx=all-treated patient population; New-Rx=new prescription patient population. Presented at the Fall Clinical Dermatology Conference - 36th Anniversary • Las Vega, Nevada • October 12 – 15, 2017 Long-term Safety and Effectiveness of Adalimumab for Moderate to Severe Psoriasis: Results from the Eight-Year Interim Analysis of the ESPRIT registry Diamant Thaçi,1 Alan Menter,2 Jashin J. Wu,3 Dilek Arikan,4 Hartmut Kupper,5 Mareike Bereswill,5 Wendell C. Valdecantos4 1Comprehensive Center for Inflammation Medicine, University Medical School Schleswig Holstein, Campus Lübeck, Germany; 2Division of Dermatology, Baylor University Medical Center, Dallas, TX, United States; 3Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, United States; 4AbbVie Inc., North Chicago, IL, United States; 5AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany INTRODUCTION • Adalimumab (ADA), a fully human, recombinant, monoclonal antibody directed against tumor necrosis factor-α (TNF-α), is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.1 • ESPRIT (NCT00799877) is an ongoing, 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator ADA prescribed in routine clinical practice according to local product labeling for adult patients with chronic plaque psoriasis.2 OBJECTIVE • To report the interim analysis of long-term safety and effectiveness of ADA treatment over the initial 8 years of the ESPRIT registry (26 September 2008–30 November 2016). MATERIALS & METHODS STUDY DESIGN AND PATIENTS • Enrollment: – Patient enrollment was initiated on 26 September 2008 and completed on 8 November 2012. – As of 30 November 2016, 6066 patients were enrolled and 6045 patients were analyzed in the ESPRIT registry. – Study sites were located in the United States, Canada, Austria, the Czech Republic, Denmark, France, Germany, Greece, Ireland, the Netherlands, Spain, Sweden, and the United Kingdom. • Treatment: ADA was dosed as recommended in the local product label. • Main inclusion criteria (Figure 1): – Adult patients (≥18 years) with chronic plaque psoriasis who have been prescribed ADA according to local product labeling and meet one of the following criteria: ■ Previously initiated ADA therapy and continued on ADA with no more than 70 consecutive days off drug. • The initial ADA dose was received either in a preregistry feeder clinical trial or from an existing prescription outside of a pre-registry feeder trial. • Source documentation of serious adverse events (SAEs), AEs of special interest, and dosing information since the initiation of therapy could be provided by the physician. ■ Newly initiated ADA therapy within 4 weeks of registry entry. STATISTICAL ANALYSES • Populations (Figure 1): – All-treated (All-Rx) patient population: Patients who received at least 1 dose of ADA in the registry and were analyzed. ■ New-prescription (New-Rx) patient population: Patients who newly initiated ADA within 4 weeks prior to registry enrollment. • Descriptive statistics are presented for baseline patient demographics and disease characteristics. Figure 1. Study Design and Patient Population of ESPRIT Observational Registry ESPRIT Registry (P10-023); Start Date: Sep 2008 Adalimumab treatment per local product label 1 2 3 4 106 9875 ** ** * * * * * * * * * * * * * * * * * * 0 Enrollment, y Newly initiated adalimumab Initial dose ≤4 wk pre-registry • New prescription (New-Rx) patients (N=2554) – 1– 2– 3– 4– 5– 6 All-Treated (All-Rx) patients (N=6045)a Patients who received at least 1 dose in the registry and were analyzed Initiated adalimumab in the past Initial dose >4 wk pre-registry • Has participated in a pre-registry feeder trialb (n=386) • Has never participated in a pre-registry feeder trial (n=3105) Phase 3 M02-570 (n=1) Jun 2003 REVEAL M03-656 (n=3) Dec 2004 BELIEVE M10-060 (n=73) Nov 2007 Phase 3 M06-808 (n=1) Jun 2006 CHAMPION M04-716 (n=2) Jul 2005 PRIDE W10-151 (n=62) Sep 2007 OLE c M03-658 (n=196) May 2004 REACH M10-405 (n=23) Aug 2008 PROGRESS M10-238 (n=25) Jan 2008 aStart dates are shown for clinical trials. bREVEAL and CHAMPION were among the feeder trials for the OLE; the number of patients in these trials was counted separately from the 196 patients in the OLE. *Patients were evaluated 3 and 6 months post enrollment, then every 6 months for ≤10 years. Patients are followed at intervals determined by routine clinical practice or as recommended by national guidelines. Safety data are captured during the entire study period. Patients who discontinue registry drug are encouraged to remain in the registry. OLE=open-label extension. • SMR was 0.34 (95% CI, 0.25–0.46) for All-Rx and 0.38 (95% CI, 0.22–0.62) for New-Rx, indicating that the observed number of deaths was below expected for age-, sex-, and country-matched population (Figure 4). Figure 4. Standardized Mortality Ratios (SMRs), Overall and by Gender (All-Rx and New-Rx Patient Populations) 0.01 0.1 1 A ll- R x p o p u la ti o n 0.28 0.410.18 0.47 0.740.28 0.34 0.460.25 Men Women Total 0.01 0.1 1 Standardized Mortality Ratio (95% CI) N e w -R x p o p u la ti o n 0.30 0.600.13 0.52 1.020.22 0.38 0.620.22 Men Women Total Death rate lower than expected Death rate higher than expected N PY Expected Observed deaths, n deaths, n 3485 12236.8 86.6 24 2560 7423.2 40.2 19 6045 19660.0 126.8 43 1376 4263.7 26.4 8 1178 2797.5 15.4 8 2554 7061.2 41.8 16 All-Rx=all-treated patient population; New-Rx=new prescription population; PY=patient-years. SAFETY • The incidence rates (E/100PY) of All-TEAEs of interest in All-Rx patients by periods of overall exposure to ADA at the time of AE onset remained stable over time (Table 3). Table 3. Incidence Rates of All-TEAEs of Interest by Periods of Overall Exposure to ADA (All-Rx Patient Population) Overall exposure to ADA at the onset of AE (years) Overall0 – <1a 1 – <2 2 – <3 3 – <4 4 – <5 5 – <6 6 – <7 7– <8 8 –<9 ≥9b AE of Interest N= 6045 4779 3995 3470 2983 2461 1943 1347 671 324 6045 E (E/100PY) PY= 5363.0 4347.6 3716.8 3221.1 2738.3 2192.2 1660.8 1020.3 485.6 522.1 25268.1 AE 1724 (32.1) 923 (21.2) 877 (23.6) 753 (23.4) 459 (16.8) 299 (13.6) 222 (13.4) 130 (12.7) 68 (14.0) 93 (17.8) 5548 (22.0) AE leading to d/c of ADA 164 (3.1) 72 (1.7) 61 (1.6) 47 (1.5) 40 (1.5) 15 (0.7) 19 (1.1) 7 (0.7) 3 (0.6) 8 (1.5) 436 (1.7) Serious AE 249 (4.6) 186 (4.3) 189 (5.1) 152 (4.7) 130 (4.7) 80 (3.6) 65 (3.9) 40 (3.9) 20 (4.1) 31 (5.9) 1142 (4.5) Serious infection 64 (1.2) 41 (0.9) 41 (1.1) 28 (0.9) 32 (1.2) 20 (0.9) 12 (0.7) 6 (0.6) 4 (0.8) 8 (1.5) 256 (1.0) Oral Candidiasis 7 (0.1) 1 (<0.1) 1 (<0.1) 0 0 0 0 0 0 0 9 (<0.1) Active tuberculosis 3 (<0.1) 0 1 (<0.1) 0 1 (<0.1) 0 0 0 0 0 5 (<0.1) Opportunistic infection, otherc 1 (<0.1) 0 0 0 1 (<0.1) 0 2 (0.1) 0 0 0 4 (<0.1) Malignancy 54 (1.0) 46 (1.1) 41 (1.1) 37 (1.1) 35 (1.3) 20 (0.9) 22 (1.3) 14 (1.4) 6 (1.2) 7 (1.3) 282 (1.1) Congestive heart failure 3 (<0.1) 1 (<0.1) 2 (<0.1) 3 (<0.1) 2 (<0.1) 0 1 (<0.1) 0 0 0 12 (<0.1) Lupus-like reactions and systemic lupusd 6 (0.1) 0 0 4 (0.1) 0 0 0 0 0 0 10 (<0.1) Demyelinating disorder 2 (<0.1) 0 2 (<0.1) 0 0 1 (<0.1) 0 0 0 0 5 (<0.1) AE leading to death 8 (0.1) 12 (0.3) 6 (0.2) 5 (0.2) 2 (<0.1) 2 (<0.1) 4 (0.2) 2 (0.2) 3 (0.6) 0 44 (0.2) aThe AEs collected from rollover patients during feeder studies most likely occurred in the first years of overall exposure to adalimumab. A closer AE documentation in feeder studies is expected compared with registry AE collection and retroactive collection of AEs for patients who initiated adalimumab therapy outside of an AbbVie clinical trial before the registry. bPatients with ≥9 years of overall exposure to adalimumab are a selected subgroup from the overall population who had longest exposure to adalimumab and potentially had a longer duration of disease. cExcluding oral candidiasis and tuberculosis. dThere were no reports of drug-induced lupus among the 7 patients with 10 events of lupus-like reactions and systemic lupus during the registry. All-TEAE=All treatment-emergent adverse event; All-Rx=all-treated patient population; AE=adverse event; ADA=adalimumab; d/c=discontinuation. EFFECTIVENESS • 45.0%–65.5% of All-Rx and 50.0%–64.2% of New-Rx patients achieved a PGA score of “clear” or “minimal” during years 1–8 of registry participation (Figure 5). Figure 5. Proportion of Patients Achieving PGA “Clear” or “Minimal” Over Years 1–8 (All-Rx and New-Rx Patient Populations: as Observed) 12 24 36 48 60 72 84 96 0 20 40 60 80 100 Registry Participation, months P a ti e n ts ,% 57.0 58.7 59.1 62.6 61.9 63.8 65.5 45.0 n= Na= New-Rx (N=2554)All-Rx (N=6045) 52.8 55.5 56.3 59.5 59.9 63.2 64.2 50.0 2635 4624 983 1862 2376 4048 881 1588 2090 3537 767 1363 1994 3185 724 1216 1496 2415 571 953 1114 1745 425 673 428 653 217 338 9 20 8 16 Na=number of patients with non-missing PGA data at the respective visit; All-Rx=all-treated patient population. New-Rx=new prescription population; PGA=Physician Global Assessment. RESULTS (continued) DISCLOSURES & ACKNOWLEDGMENTS D. Thaçi has received honoraria from AbbVie, Amgen, Biogen-Idec, Celgene, GSK, Dignity, Janssen, Leo, Maruho, Mitsubishi, Lilly, Novartis, Pfizer, Regeneron/Sanofi, and UCB for participation on advisory boards, as a speaker, and for consultancy; and received research grants from AbbVie, Biogen-Idec, Leo, and Pfizer. A. Menter has received grants and honoraria from AbbVie, Amgen, Janssen Biotech, Inc., and Leo Pharma for service on an advisory board, as consultant, investigator, and speaker; received grants and honoraria from Allergan for service on an advisory board and as a consultant and from Eli Lilly for service on an advisory board and as a consultant and investigator; received grants and honoraria from Boehringer Ingelheim for service on an advisory board and as an investigator; received grants and honoraria from Novartis and Pfizer for service as a consultant and investigator; received grants from Celgene, Dermira, Merck, Neothetics, Regeneron, and Syntrix for service as an investigator; and received honoraria from Galderma for service as a consultant. J. J. Wu is an investigator for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and Regeneron. D. Arikan, H. Kupper, M. Bereswill, and W. C. Valdecantos are full-time employees of AbbVie and may own stock/options. AbbVie funded the ESPRIT study (NCT00799877), contributed to its design, and participated in data collection, analysis, and interpretation of the data and in writing, review, and approval of this presentation. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVie and Richard M. Edwards, PhD, and Janet Matsuura, PhD, of Complete Publication Solutions, LLC (North Wales, PA, USA). AbbVie funded the medical writing support. CONCLUSIONS ■ No new safety signals were observed with ADA treatment during this 8-year interim analysis, and safety was consistent with the known safety profile of ADA. ■ Incidence rates of serious infections and malignancies remained stable with up to >8 years of overall exposure to ADA. ■ The number of treatment-emergent deaths in the registry was below the expected rate compared with the general population. ■ As-observed effectiveness of ADA remained stable through 96 months. REFERENCES 1. Humira® (adalimumab). Full Prescribing Information, AbbVie Inc., North Chicago, IL, 2016. 2. Menter A, et al. J Am Acad Dermatol. 2015;73(3):410-19.e6. FC17PosterAbbVieThaciLongTermSafety8YearInterim.pdf